5.30487

StemSelect PD 0332991

• Synonym(s): StemSelect PD 0332991, 6-Acetyl-8-cyclopentyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one, HCl, Cdk4/Cdk6 Inhibitor V, PD-0332991, HCl, PF-332991, HCl
• Empirical Formula (Hill Notation): C₂₄H₂₉N₇O₂ · xHCl
• CAS Number: 827022-32-2
• Molecular Weight: 447.53 (free base basis)
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• assay: ≥97% (HPLC)
• Quality Level: 100
• form: liquid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; avoid repeated freeze/thaw cycles; protect from light
• color: yellow
• solubility: water: 10 mg/mL
• storage temp.: −70°C
• InChI: 1S/C24H29N7O2.ClH/c1-15-19-14-27-24(28-20-8-7-18(13-26-20)30-11-9-25-10-12-30)29-22(19)31(17-5-3-4-6-17)23(33)21(15)16(2)32;/h7-8,13-14,17,25H,3-6,9-12H2,1-2H3,(H,26,27,28,29);1H
• InChI key: STEQOHNDWONVIF-UHFFFAOYSA-N

Description

General description

A cell-permeable, orally available and brain permeant, non-toxic pyridopyrimidinone compound that acts as a potent, selective, reversible, ATP competitive inhibitor of Cdk4 and Cdk6 (IC₅₀ = 11, 9, and 15 nM for Cdk4/D1, Cdk4/D3 and Cdk6/D2, respectively). Hence, it reduces retinoblastoma protein phosphorylation at Ser780/Ser795 (IC₅₀ = 66 nM in MDA-435 cells) and arrests cell cycle at G1 phase. Acts as a cytostatic agent, but does induce apoptotic cell death when used alone. However, it potentiates the cytotoxicity of dexamethasone (>Cat. No. 265005), bortezomib (>Cat. No. 504314), and tamoxifen (Cat. No. 579000) in estrogen receptor (ER)-positive cell lines. Exhibits only a trivial inhibitory activity towards Cdk2/E2, Cdk2/A, Cdk1/B and Cdk5/p25 in a 36-kinase panel (IC₅₀ >10 µM). Improves endoderm differentiation of late G1-human embryonic stem cells expressing Smad2 or Smad3 (~ 750 nM) and further enhances endoderm differentiation into hepatic and pancreatic progenitor cells. Shown to regress the growth of human breast tumor xenografts in murine models (~150 mg/kg, p.o., daily).

A cell-permeable, orally available and brain permeant, non-toxic pyridopyrimidinone compound that acts as a potent, selective, reversible, ATP competitive inhibitor of Cdk4 and Cdk6 (IC₅₀ = 11, 9, and 15 nM for Cdk4/D1, Cdk4/D3 and Cdk6/D2, respectively). Hence, it reduces retinoblastoma protein phosphorylation at Ser780/Ser795 (IC₅₀ = 66 nM in MDA-435 cells) and arrests cell cycle at G1 phase. Acts as a cytostatic agent, but does induce apoptotic cell death when used alone. However, it potentiates the cytotoxicity of dexamethasone (>Cat. No. 265005), bortezomib (>Cat. No. 504314), and tamoxifen (Cat. No. 579000) in estrogen receptor (ER)-positive cell lines. Exhibits only a trivial inhibitory activity towards Cdk2/E2, Cdk2/A, Cdk1/B and Cdk5/p25 in a 36-kinase panel (IC₅₀ >10 µM). Improves endoderm differentiation of late G1-human embryonic stem cells expressing Smad2 or Smad3 (~ 750 nM) and further enhances endoderm differentiation into hepatic and pancreatic progenitor cells. Shown to regress the growth of human breast tumor xenografts in murine models (~150 mg/kg, p.o., daily).

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Cdk4 & Cdk6

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Pauklin, S. and Vallier, L., 2013. Cell155, 135.
Finn, R.S., et al. 2009. Breast Cancer Res.11, R17.
Menu, E., et al. 2008. Cancer Res.68, 5519.
Baughn, L.B., et al. 2006. Cancer Res.66, 7661.
Fry, D.W., et al. 2004. Mol. Cancer Ther.3, 1427.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable